Hybrid, planar optofluidic integration

ABSTRACT

An optofluidic platform is constructed to comprise a vertical integration of optical and fluidic layers. The optical layer enables interaction of light with a fluid for a variety of purposes, including particle detection, manipulation, and analysis. The vertical integration allows layers to be permanently or temporarily attached to each other. Temporary attachments provide the advantage of reusing the same optical layer with different fluidic layers. Most preferably, the optical layer comprises antiresonant reflecting optical waveguide. Further, a fluidic layer can be configured to act as an interface between the optical layer and other fluidic layers attached thereon. Moreover, the fluidic layers can be configured to perform fluidic functions. The optofluidic platform can also comprise a protective layer. As such, a liquid solution can be introduced in the optofluidic platform and single particles contained therein can be optically detected with extremely high sensitivity and without the need for advanced microscopy equipment.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No. 13/988,253 filed May 17, 2013, which is a National Stage of International Application No. PCT/US2011/061463 filed Nov. 18, 2011, which claims benefit under 35 U.S.C. §119(e) to U.S. Provisional Application 61/415,467 filed Nov. 19, 2010, the contents of each are hereby incorporated by reference in their entirety.

TECHNICAL FIELD

The present invention relates generally to the field of integrated optics, and more particularly to an optofluidic platform for optical particle detection without the need for advanced microscopy equipment. The optofluidic platform comprises a vertical integration of an optical layer and a plurality of fluidic layers. The optical layer can employ antiresonant reflecting optical waveguides, known as ARROWs or ARROW waveguides. Further, the fluidic layer can be configured to perform fluidic functions on liquids introduced into the optofluidic platform. The optofluidic platform can also comprise a protective layer.

BACKGROUND

Optofluidics is a rapidly growing field that deals with the interplay of optics and fluids, typically liquids, at the microscale. Currently, the major research trends include optical devices defined by fluids, optical particle manipulation in liquids, and optical particle detection and analysis, especially in biology and biomedicine.

It has been pointed out that one of the main advantages of an optofluidic approach is the possibility to vertically combine layers with different functionalities in a single device. Proof-of-principle demonstrations include fluidically tunable waveguide transmission [1] and combination of electrical and fluidic layers [2].

SUMMARY

Here, we describe a novel approach to optofluidic integration based on liquidcore waveguides. Its novel features are:

use of liquid-core waveguide layer featuring fully planar optical beam paths for vertical integration;

use of dissimilar materials to achieve desired functionalities in individual layers. Examples include silicon, PDMS, glass;

reconfigurable assembly of vertically integrated optofluidic system.

In a presently preferred embodiment of the invention, an optofluidic platform is constructed so as to comprise a vertical integration of optical and fluidic layers. The optofluidic platform can also comprise a protective layer. The vertical integration allows layers to be permanently or temporarily attached to each other. Temporary attachments provide the advantage of reusing the same optical layer with different fluidic layers.

In an embodiment, the optical layer can comprise a self-contained, planar optofluidic platform for optical particle detection with extremely high sensitivity but without the need for advanced microscopy equipment. In a further embodiment, the optical layer can comprise hollow-core antiresonant reflecting optical waveguides (ARROWs), solid-core ARROWs, and fluidic reservoirs. The configuration of the different components within the optical layer can allow liquids to be introduced into the hollow-core ARROWs and sub-picoliter volumes thereof to be optically excited for single particle detection.

In an embodiment, a fluidic layer can be attached to the optical layer and can act as a gasket that provides a seal for liquids between the protective layer and the optical layer. In a further embodiment, the fluidic layer attached to the optical layer can be configured to restore the optical waveguide properties of the optical layer and can act as an interface layer between the optical layer and other fluidic layers attached thereon. Additionally, the fluidic layers can be configured to perform fluidic functions, such as filtering and distributing to the optical layer liquids introduced at the protective layer.

In an embodiment, the protective layer can be attached to a fluidic layer. The protective layer can be configured to introduce liquids into the optofluidic platform using syringes and syringe pumps.

In an embodiment, the optical layer can be fabricated by depositing dielectric layers on a silicon substrate, using a sacrificial material to pattern a desired hollow-shape, covering the sacrificial material with additional dielectric layers, and using chemical etching to remove the sacrificial materials. Additionally, a fluidic layer can be made of polydimethylsiloxane, polymers, or glass materials. The protective layer can be made of acrylic glass. These layers can be permanently connected via standard oxygen plasma bonding or can be assembled with a temporary fixture under pressure.

Other aspects of illustrative embodiments of the invention are described below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a planar optofluidic platform; (a) shows a schematic layout, images of waveguide cross sections and completed chip; (b) shows a key micro fabrication process steps for creating liquid core waveguides.

FIG. 2 shows integration of a fluidic layer; (a) shows a schematic side view of optofluidic layer sequence; (b) shows a top view of completed assembly with Luer connections; (c) shows a fluorescence image of quantum dots pipeted into one PDMS opening and vacuumed through liquid-core waveguide into opposing opening.

FIG. 3 shows a vertical optofluidic integration; (a) shows a schematic side view of multilayer hybrid optofluidic integration with dedicated functional optical and fluidic layers (dashed lines: channels; particle flow as indicated); (b) shows a cross-sectional view of structure showing air gaps in PDMS layer 1 to maintain optical waveguiding.

FIG. 4 shows a vertical optofluidic integration: sample delivery; (a) shows a sample mixed and distributed into three optical waveguides (white: microfluidic channels in PDMS layer); (b) shows three samples distributed into three optical waveguide channels. Note: PDMS 1 not shown for clarity.

FIG. 5 shows a vertical optofluidic integration: sample filtering; (a) shows an overview of filter location (dashed parallelogram) in fluidic layer; (b) shows a close-up view of the filter section with PDMS posts providing mechanical barriers for large analyte components.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

We have invented a planar, optofluidic approach that is based on liquid-core optical waveguides that maximizes the interaction between light and sample analytes. Based on creating hollow-core antiresonant reflecting optical waveguides (ARROWs), we have developed a self-contained, planar optofluidic platform for optical particle detection with extremely high sensitivity but without the need for advanced microscopy equipment [3]. The basic layout of this platform along with the fabrication steps for forming the hollow-core waveguides are shown in FIG. 1.

The scanning electron image in the bottom center of FIG. 1 shows a cross section of such a waveguide with hollow-core dimensions of 5×12) lm. In addition, solid-core ARROW waveguides (see SEM in bottom right of FIG. 1 a) are connected to different points of the liquid core. This creates separate access paths for liquids and light into the main channel, and can also be used to define optical excitation areas with sub-picoliter volumes to achieve single molecule sensitivity. FIG. 1 a depicts a typical experimental layout in which excitation light (green; arrow pointing into the optofluidic platform) enters the liquid core through an orthogonally intersecting solid-core ARROW. Generated light (red; arrow pointing out from the optofluidic platform) is collected perpendicularly in the chip plane and guided to the chip edges for detection. Fluidic reservoirs at the channel ends allow for easy channel filling and insertion of electrodes to induce electrokinetic particle movement. The photograph in the bottom left of FIG. 1 a illustrates the compact size of a completed optofluidic chip.

The fabrication process shown in FIG. 1 b includes (i) deposition of dielectric layers (e.g. SiO2 and SiN) of the correct thickness on a silicon substrate; (ii) patterning of a sacrificial material (e.g. SU-8) into the desired hollow-core shape; (iii) covering the sacrificial layer with additional ARROW guiding layers; and (iv) removal of the sacrificial core with chemical etching after exposing ends by plasma etching. It can be used flexibly to define a variety of optical and fluidic layouts with microscale precision.

The platform depicted in FIG. 1 has successfully been used for detection and analysis of a variety of molecules, including fluorescence detection of single dye molecules, fluorescence correlation analysis of liposomes and ribosomes, and surface-enhanced Raman detection of rhodamine 6G molecules [3].

We have also carried out a proof-of-principle study on hybrid vertical alignment of optofluidic layers. The key intention was to establish that the silicon-based ARROW chip can be combined with materials such as polydimethylsiloxane (PDMS), polymers, or glass that are traditionally used for micro fluidic devices. FIG. 2 a shows a side view schematic of this test approach. A PDMS layer is attached on top of the ARROW chip followed by a cover of acrylic plastic. This PDMS layer acts as a gasket that provides a seal for liquids between the acrylic and silicon layers by conforming to the elevated waveguide structures on chip (see FIG. 1).

In order to achieve this function, PDMS was prepared in accordance with standard soft lithography methods and poured directly onto the ARROW chip. Temporary standoff cylinders were placed over the openings to the liquid-core ARROW to create through holes in the PDMS and removed after the PDMS was thermally cured. Channels were drilled into the acrylic piece and terminated with Luer connection for introduction of liquids into the liquid-core waveguides using syringes and syringe pumps. (FIG. 2 b). FIG. 2 c shows a top down image of the chip without the top acrylic piece. Fluorescent dye was introduced into one of the PDMS holes and vacuumed through the waveguide into the opposite opening. The observation of bright red fluorescence only in the two reservoirs demonstrates that this basic microfluidic functionality was successfully implemented without any leaks between PDMS and ARROW chip.

A multilayered approach to optofluidic integration has the advantage that each layer can be optimized for its desired functionality. While our silicon-based devices have shown excellent optical properties, they are not ideal from a packaging standpoint. One possible preferred approach to hybrid integration is to combine fluidic and optical layers in a single device as shown in FIG. 3 a. The preferred implementation combines the silicon-based optical layer with two fluidic layers of soft polydimethylsiloxane (PDMS), capped by a hard access layer (e.g. acrylic plastic) for attaching fluidic connections (syringes, pumps). These layers can either be permanently connected via standard oxygen plasma bonding or can be assembled with a temporary fixture under pressure. The latter approach has the advantage that layers can be swapped, e.g. different fluidic channel designs can be used with a single optical chip.

Direct casting of PDMS on an ARROW chip has the disadvantage of placing high-refractive-index PDMS on top of the ARROW waveguides and destroying the optical waveguiding properties. The multilayer approach overcomes this problem since the first PDMS layer will contain air channels that follow the shape of the waveguide geometry in the areas that are critical for optical guiding. This results in air gaps around the waveguides that restore the required index profile as illustrated in FIG. 3 b.

A second step can add the second PDMS layer (PDMS2) and demonstrate essential fluidic device functions in this layer such as sample distribution and mechanical filtration. FIG. 4 shows two preferred example implementations of sample distribution layouts (Note that PDMS1 layer is not shown for clarity). In FIG. 4 a, the PDMS2 layer is designed as a 1-in-3 distributor for loading three ARROW waveguides with the same sample mixture. FIG. 4 b, on the other hand, represents a 3-in-3 input configuration where three different sample mixtures can be investigated in three waveguide channels simultaneously. Both implementations enable multiplexing capabilities of the detection platform, albeit in different ways. Many more configurations are conceivable, in particular as the number of liquid-core waveguides grows. Note again that very different functionality is achieved with the same underlying optical ARROW layer. When the device is assembled without permanent bonding, this makes the platform highly customizable and reconfigurable.

Sample preparation is a constant concern in microfluidic systems. One example for such a functionality is a mechanical fluidic filtering step that separates large cell components from molecular level targets after an off-chip lysing process. The constraints in our case are set by the liquid-core waveguide dimensions in the optical layer which are typically on the order of 5×12 μm. In order to remove all analyte contents larger than 3 μm, a pillar-based filter structure can be added to the input manifold in the PDMS2 layer as shown in FIG. 5. The necessary resolution of a few microns can be easily achieved using SU-8 mold lithography. 

1. An optofluidic device comprising: an optical layer comprising optical waveguides, the optical waveguides comprising hollow-core waveguides and solid-core waveguides, the hollow-core waveguides and the solidcore waveguides configured to intersect perpendicularly; fluidic layers configured to provide fluidic functions; a protective layer; means for attaching the optical layer to the fluidic layers; means for restoring optical indexes of the optical waveguides; means for attaching the fluidic layers to the protective layers; means for injecting sample liquid into the hollow-core waveguides through the protective means for applying fluidic functions to the injected sample liquid through the fluidic means for injecting light into the solid-core waveguides, wherein the injected light is guided within the solid-core waveguides and through the sample liquid injected in the hollowcore waveguides.
 2. The device of claim 1, wherein the optical waveguides comprise ARROWs.
 3. The device of claim 1, wherein the fluidic functions comprise distribution of sample liquids and filtering of sample liquid contents.
 4. The device of claim 1, wherein the protective layer comprises means for introducing liquid samples using syringes and syringe pumps.
 5. The device of claim 1, wherein the means for attaching the optical layer to the fluidic layers comprise permanent or temporary attachment means.
 6. The device of claim 1, wherein the means for restoring the optical indexes comprises an air gap between the optical waveguides and an attaching fluidic layer of the fluidic layers.
 7. The device of claim 1, wherein the means for attaching the fluidic layers to the protective layers comprise permanent or temporary attachment means. 